7. Project Summary/Abstract Parkinson?s disease (PD) affects over six million individuals globally. With increasing life expectancy, this number is estimated to double by 2040. The impaired ability to sustain a steady motor performance is a major cause of morbidity in patients with PD. This is characterized by a rapid progressive decrement in the speed, amplitude, or force of movements during continuous tasks (e.g., walking, writing). The standard pharmacological and surgical therapies are ineffective in improving the decrement. There is a need for novel targeted therapies with minimal adverse effects for better symptom control. The goal of the proposed mentored research project is to assess the effects of functional magnetic resonance imaging (fMRI)-based neurofeedback intervention on brain plasticity and sustained motor performance in patients with PD. FMRI- based neurofeedback is a noninvasive intervention that improves individuals? abilities to control their brain activity in real-time. With practice, individuals can also learn how to self-regulate behavior that is associated with this brain activity. This intervention has been used successfully in several neuropsychiatric disorders (e.g., anxiety, addiction), but reports of its use in PD are scant. Using fMRI-based neurofeedback combined with motor imagery, we will train patients with PD to increase the functional connectivity strength between their right insula and dorsomedial frontal cortex. These brain regions are important in initiating and sustaining voluntary movement and are affected by the pathological process in PD. We will examine the effects of this training on resting-state functional connectivity of brain networks and on motor performance. This proposal is in line with the NINDS mission to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. If successful, this neurofeedback-guided motor imagery training could be incorporated into rehabilitation programs in PD. Candidate: Dr. Tinaz is a movement disorders neurologist. Her career goal is to develop a research program to study the neural basis of movement disorders, specifically PD, identify targets for novel therapies, and investigate the brain changes in response to interventions using neuroimaging. Dr. Tinaz seeks additional training in advanced fMRI methodology including neurofeedback, behavioral intervention development, biostatistics, and in design and conduct of clinical trials via didactic courses and hands-on learning. The project and career development plan will prepare her to design large-scale clinical trials to assess the efficacy of neurofeedback intervention in PD. Environment: The research and training activities will take place at Yale School of Medicine. The Magnetic Resonance Research Center at Yale is a state-of-the-art facility providing the infrastructure and interdisciplinary expertise for neuroimaging research. Dr. Tinaz?s mentors and consultants are experts on fMRI and clinical trial methodology. Upon completion of the proposed project, Dr. Tinaz will be well poised to become an independent clinician-scientist combining her expertise in movement disorders neurology and neuroimaging.